The future of HIV treatment

Before 1996 there was only one class of anti-HIV drugs available. Combination therapy for HIV, as we now know it, did not exist. In those days the outlook for people with HIV was poor. However, looking at the different anti-HIV drugs available today, it’s clear that in a relatively short space of time major advances in HIV treatments have been made.

There still isn’t a cure for HIV, and it doesn’t look likely that there will be for many years yet. However, new and novel treatments for controlling HIV are being developed all the time. New treatments are helping to reduce the number of pills people with HIV need to take every day, and are also being designed to be effective for people who have resistance to many of the drugs currently available. Some newer anti-HIV drugs are also being developed which are active at lower doses, potentially giving fewer or less severe side effects.

As well as the development of new anti-HIV drugs from the current available classes, new and novel approaches to HIV treatment are on the horizon. Below we give an overview of some new HIV treatments that are either in development or have recently become generally available.

Integrase inhibitorsUntil recently, treatments for HIV only targeted two of three enzymes used by HIV to replicate; reverse transcriptase and protease. Integrase inhibitors are an entirely new class of anti-HIV drugs designed to target the third enzyme HIV uses to replicate known as integrase. Integrase is used by HIV to insert (or integrate) its genetic code (viral DNA) into the human DNA in a CD4 cell. The aim of integrase inhibitors is to stop this process which in turn stops HIV from making copies of itself. The first drug in this class to become widely available in the UK was Raltegravir, and it has been shown to be effective both for people who have never taken any anti-HIV drugs before, and in people who are resistant to many of the drugs that are currently available. A second drug in this class, Elvitegravir, is also showing promise and is currently in clinical trials [1].

CCR5 antagonistsThis class of drugs are a type of entry inhibitor in that they prevent HIV from attaching to and therefore entering CD4 cells. They do this by blocking one of the receptors (known as the CCR5 co-receptor) on CD4 cells that HIV needs to attach to in order to gain entry to the cell. Maraviroc was the first CCR5 antagonist to become widely available in the UK. It has been shown to be effective in people resistant to many of the other anti-HIV drugs currently available, as well as people who have no resistance to any anti-HIV drugs [2].

Maturation inhibitorsThe idea behind maturation inhibitors is to prevent new HIV copies from developing into mature viral particles at the end of the replication process in a CD4 cell. The viral particles produced would then be defective and unable to then go on to infect other CD4 cells. The first maturation inhibitor in development is Bevirimat (formerly known as PA-457) which is derived from betulinic acid, found in the bark of many trees. As with the other new classes of drugs in development, it is hoped that maturation inhibitors will be effective in people who have resistance to many of the anti-HIV drugs currently available. However, it will probably be a few years until the first maturation inhibitor becomes generally available.

Therapeutic vaccinesTherapeutic vaccines are different from preventative vaccines which aim to protect people against being infected with a virus in the first place. The idea behind therapeutic vaccines is to stimulate your immune system against HIV that is already present, enabling your own immune system to control your HIV infection.

The advantage of therapeutic vaccines would in theory be that you would not need to take anti-HIV drugs every day. A simple injection every week or month, for example, could be sufficient to enable your own immune system to control HIV without the need for powerful drugs. This would also mean that people with HIV wouldn’t have to cope with the toxicity and side effects of the current anti-HIV drugs.

Studies to find therapeutic vaccines have been ongoing for many years, and although some have appeared promising it will still probably be many years until an effective and affordable therapeutic vaccine becomes available [3].

You can read an A to Z of investigational drugs on NAM's website, www.aidsmap.com.

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